Abstract Details

Title Immunotherapies Improve Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-008

Objective

This study evaluated the effect of multiple sclerosis (MS) immunotherapy on long-term disability outcomes.

Background

The effect of MS immunotherapy on relapses and short-term disability outcomes has been established in randomised clinical trials. However, their long-term effectiveness is not well documented.

Design/Methods

Using the MSBase registry, we identified patients followed for ≥1 year, with ≥3 EDSS scores, ≥1 EDSS score per year, and exposed to an MS therapy. Marginal structural models, re-weighted in 6-monthly intervals with stabilised inverse probability of treatment weights, adjusted for visit frequency and nested within MS centres, were built to evaluate cumulative hazards of relapses, and 12-month confirmed disability worsening and improvement events.

Results

24,884 patients were included (cumulative follow-up 177,227 years, 71% female, mean age (at first visit) 36 years, mean MS duration 3 years, median EDSS 2). Immunotherapy was associated with 45% reduction in the incidence of relapses (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.61). The effect of treatment declined with age (-1% per year), disability (-14% per EDSS step), the number of prior therapies (-24% per therapy) secondary progressive MS (-68%), recent disability worsening (-20%), and recent on-treatment relapses (-55% per relapse), especially severe relapses (-66%). The effect on relapses was heightened in CIS (+58%).

Patients on immunotherapies were 26% less likely to experience worsening of disability than those untreated (HR 0.74, CI 0.62-0.87). This association declined with greater disability (-8% per EDSS step), recent on-treatment disability worsening (-14%) and recent on-treatment relapses (-43% per relapse).

Treated patients were 39% more likely to experience improvement of disability (HR 1.39, CI 1.22-1.59). This effect declined with age (-2% per year), disease duration (-6% per year), and disability (-8% per EDSS step). It was potentiated in CIS (+70%) and in patients with recent relapses (+53%).

Conclusions

Sustained MS immunotherapy reduces long-term disability accrual by approximately 26%.

Authors/Disclosures
Tomas Kalincik PRESENTER	Tomas Kalincik has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Tomas Kalincik has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Health and Medical Research Council. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MS Research Australia. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Tomas Kalincik has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for WebMD Global. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BioCSL. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Tomas Kalincik has received research support from Biogen. The institution of Tomas Kalincik has received research support from Novartis. The institution of Tomas Kalincik has received research support from Genzyme. The institution of Tomas Kalincik has received research support from Roche. The institution of Tomas Kalincik has received research support from Celgene. The institution of Tomas Kalincik has received research support from Merck. The institution of Tomas Kalincik has received research support from MSBase Foundation. The institution of Tomas Kalincik has received research support from ARSEP and EDMUS Foundations. The institution of Tomas Kalincik has received research support from MS Research Australia. The institution of Tomas Kalincik has received research support from National Health and Medical Research Council. The institution of Tomas Kalincik has received research support from Australian Research Council. The institution of Tomas Kalincik has received research support from MS Society. The institution of Tomas Kalincik has received research support from Trish Foundation. Tomas Kalincik has a non-compensated relationship as a scientific leadership group chair with MSBase Foundation that is relevant to �鶹��ýӳ�� interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Eva Havrdova, MD (Neurologicka Klinika 1 LF UK)	Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
Maria Trojano (Policlinico - Bari)	Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi_Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen.
Guillermo Izquierdo Ayuso, MD (Servicio De Neurologia)	Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer, Biogen Idec, Novartis, Sanofi, Merck Serono, Roche, Actelion and Celgene. Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme, Novartis, Sanofi Aventis, Alexion.
	No disclosure on file
Marco Onofrj, MD	Dr. Onofrj has nothing to disclose.
Alessandra Lugaresi, MD (Istituto delle Scienze Neurologiche di Bologna)	Dr. Lugaresi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis Pharma. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Sqibb. Dr. Lugaresi has a non-compensated relationship as a Speaker at meetings, participant in trials with Fondazione Italiana Sclerosi Multipla that is relevant to �鶹��ýӳ�� interests or activities.
Alexandre Prat, MD (CHUM Hopital Norte Dame/ Dept of Neurology)	The institution of Dr. Prat has received research support from CIHR and MSSC.
J M. Girard, MD	Dr. Girard has nothing to disclose.
Pierre Duquette, MD	The institution of Dr. Duquette has received research support from Biogen and Genzyme.
Pierre Grammond, MD (Hotel-Dieu De Levis Hospital)	Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pendopharm. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Grammond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Serono. The institution of Dr. Grammond has received research support from Roche.
Francois Grand-Maison, MD (Francois Grand'Maison MD INC)	Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Serono. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Grand-Maison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis .
Patrizia Sola (Nuovo Ospedale Civile S. Agostino-Estense)	Patrizia Sola has nothing to disclose.
Diana Ferraro, MD, PhD (University of Modena and Reggio Emilia)	Dr. Ferraro has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ferraro has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Binding Site. Dr. Ferraro has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
	No disclosure on file
Raed Alroughani, MD, F�鶹��ýӳ��	Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, AstraZeneca, Novartis, Merck, Roche, Sanofi. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for AstraZeneca, Biogen, Novartis, Merck, Roche, Sanofi.
R.M.M. Hupperts, MD (Biogen Int. B.V.)	No disclosure on file
Murat Terzi, PhD (19 Mayis Universitesi)	Dr. Terzi has nothing to disclose.
Cavit Boz, MD	Dr. Boz has nothing to disclose.
Jeannette Lechner-Scott, MD, PhD, FRACP (HNEAH)	The institution of Prof. Lechner-Scott has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. The institution of Prof. Lechner-Scott has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Prof. Lechner-Scott has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Prof. Lechner-Scott has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Prof. Lechner-Scott has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for elsevier. The institution of Prof. Lechner-Scott has received research support from Merck. The institution of Prof. Lechner-Scott has received research support from Biogen.
	No disclosure on file
Vincent Van Pesch, MD, PhD (Cliniques Universitaires Saint-Luc)	Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Vincent Van Pesch, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Vincent Van Pesch, MD, PhD has received research support from Biogen.
Gerardo Iuliano, PhD (Osp Riuniti San Giovanni Di Dio)	Dr. Iuliano has nothing to disclose.
Franco Granella (Zeneca-UK)	Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Franco Granella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono.
Roberto Bergamaschi	Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Roberto Bergamaschi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi.
Ricardo Fernandez Bolanos, MD (Complejo Hospitalario Nuestra Senora de Valme)	No disclosure on file
Daniele Litterio A. Spitaleri (A.O. "S. Giuseppe Moscati")	Daniele Litterio A. Spitaleri has received research support from Novartis.
	No disclosure on file
Ostoja (Steve) Vucic, MBBS, FRACP (Concord Hosoital)	Prof. Vucic has a non-compensated relationship as a Member-Advisory Board with Biogen Idec Australia that is relevant to �鶹��ýӳ�� interests or activities. Prof. Vucic has a non-compensated relationship as a Honorarium with Merkc Serono Ausralia that is relevant to �鶹��ýӳ�� interests or activities.
Radek Ampapa, MD (Neurologicka Klinika Jihlava)	Dr. Ampapa has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Dr. Ampapa has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ampapa has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Ampapa has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzym. Dr. Ampapa has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Ampapa has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.
Pamela A. McCombe, MD (Dr PA McCombe Medical Pty Ltd)	Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. McCombe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. The institution of Dr. McCombe has received research support from Motor Neurone Disease Resaerch Institute of Australia.
Cristina M. Ramo, MD (Hospital Germans Trias I Pujol)	Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ALMIRALL . Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANDOZ. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Almirall. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOGEN. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen . Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Ramo has received research support from HORIZON-2020. The institution of Dr. Ramo has received research support from fis (SPANISH GOVERNMENT). The institution of Dr. Ramo has received research support from BIOGEN. The institution of Dr. Ramo has received research support from MERCK. The institution of Dr. Ramo has received research support from ALMIRALL. The institution of Dr. Ramo has received research support from NOVARTIS. The institution of Dr. Ramo has received research support from RICORS (Spanish Government). The institution of Dr. Ramo has received research support from ROCHE. Dr. Ramo has received publishing royalties from a publication relating to health care.
Thor Petersen (Arhus Sygehus)	No disclosure on file
Freek Verheul, MD	No disclosure on file
Julie Prevost, MD (Neurologie des Laurentides)	No disclosure on file
Francisco Javier Olascoaga Urtaza, MD	No disclosure on file
Edgardo Cristiano, MD (Hospital Italiano De Buenos Aires)	Dr. Cristiano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cristiano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Cristiano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Cristiano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Cristiano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Helmut Butzkueven, MD, MBBS	Dr. Butzkueven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oxford Health Policy Forum. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for MSBase . The institution of Dr. Butzkueven has received research support from NHMRC. The institution of Dr. Butzkueven has received research support from Biogen. The institution of Dr. Butzkueven has received research support from Roche. The institution of Dr. Butzkueven has received research support from Novartis.

�鶹��ýӳ��

�鶹��ýӳ��